title: CD28 expression by peripheral blood lymphocytes as a potential predictor of the development of de novo malignancies in long-term survivors after liver transplantation.
abstract: At present, no method is available for accurately monitoring the degree of immunosuppression induced by antirejection therapies. The aim of this study was to determine whether CD28 and CD38 expression by peripheral blood mononuclear cells could be useful in predicting the development of de novo malignancies after liver transplantation. Flow cytometry analysis was used to measure the expression of CD28 and CD38 by peripheral blood lymphocytes in 134 stable, long-term survivors of liver transplantation. Patients who developed a de novo malignancy after undergoing a medical checkup were entered into a cancer group. Twenty-two patients (16.4%) developed at least 1 de novo malignancy over a mean interval of 22 ± 14 months (1.2-49.4 months) after the checkup. The mean frequency of CD28(+)CD8(+) cells was significantly lower in the cancer group versus the noncancer group (39% ± 22 versus 51% ± 21, P = 0.008), but CD38 expression was similar in the 2 groups. Multivariate analysis indicated that an age greater than 50 years (odds ratio = 5.81) and a low frequency of CD28(+)CD8(+) cells at the time of the checkup (odds ratio =3.16) were the only significant predictors of the development of de novo malignancies (P = 0.027). The actuarial proportion of patients with de novo malignancies was significantly lower when the frequency of CD28(+)CD8(+) cells was greater than or equal to 40% instead of less than 40% (P = 0.01). Flow cytometry measurements of CD28 expression by peripheral blood lymphocytes may facilitate the identification of patients at a high risk of developing de novo malignancies. Further prospective studies are necessary to determine whether such measurements could have a place in routine clinical practice to enable the intensity of immunosuppression to be minimized in patients who have an increased risk of developing cancer.
authors.affiliation: Unité Mixte de Recherche en Santé 938, Institut National de la Santé et de la Recherche Médicale, Site Saint-Antoine, Université Paris 6, Paris, France. emmanuel.boleslawski@chru-lille.fr
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Boleslawski
authors.forename: Samia Ben
authors.initials: SB
authors.lastname: Othman
authors.forename: Lynda
authors.initials: L
authors.lastname: Aoudjehane
authors.forename: Sandrine
authors.initials: S
authors.lastname: Chouzenoux
authors.forename: Olivier
authors.initials: O
authors.lastname: Scatton
authors.forename: Olivier
authors.initials: O
authors.lastname: Soubrane
authors.forename: Yvon
authors.initials: Y
authors.lastname: Calmus
authors.forename: Nadira
authors.initials: N
authors.lastname: Delhem
authors.forename: Filomena
authors.initials: F
authors.lastname: Conti
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000097:blood; D000328:Adult; D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood; D018106:CD28 Antigens / Q000097:blood*; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D005602:France; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D053208:Kaplan-Meier Estimate; D016031:Liver Transplantation / Q000276:immunology* / Q000401:mortality; D016015:Logistic Models; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology*; D016017:Odds Ratio; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D017741:Survivors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018106:CD28 Antigens; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1